title: Gene x disease interaction on orbitofrontal gray matter in cocaine addiction.
abstract: BACKGROUND
  Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability.
  
  
  OBJECTIVE
  To examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls.
  
  
  METHODS
  Cross-sectional comparison.
  
  
  METHODS
  Clinical Research Center at Brookhaven National Laboratory.
  
  
  METHODS
  Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles).
  
  
  METHODS
  The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis × MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors.
  
  
  RESULTS
  (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls. (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use. (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables.
  
  
  CONCLUSIONS
  Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. nellyklein@bnl.gov
authors.forename: Nelly
authors.initials: N
authors.lastname: Alia-Klein
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Parvaz
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Woicik
authors.forename: Anna B
authors.initials: AB
authors.lastname: Konova
authors.forename: Thomas
authors.initials: T
authors.lastname: Maloney
authors.forename: Elena
authors.initials: E
authors.lastname: Shumay
authors.forename: Ruiliang
authors.initials: R
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.forename: Anat
authors.initials: A
authors.lastname: Biegon
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Rita Z
authors.initials: RZ
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics / Q000473:pathology / Q000523:psychology; D000483:Alleles; D001284:Atrophy; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects* / Q000473:pathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology; D012907:Smoking / Q000235:genetics / Q000523:psychology; D014029:Tobacco Use Disorder / Q000235:genetics / Q000473:pathology / Q000523:psychology
chemical_list: D018765:Dopamine Uptake Inhibitors; D008995:Monoamine Oxidase; D003042:Cocaine; D004298:Dopamine